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. 2022 Mar 29;10(7):2455-2469.
doi: 10.1002/fsn3.2852. eCollection 2022 Jul.

Ameliorated effects of a lipopeptide surfactin on insulin resistance in vitro and in vivo

Xiaoyu Chen  1 , Hongyuan Zhao  1 , Fanqiang Meng  1 , Libang Zhou  1 , Xinyi Pang  2 , Zhaoxin Lu  1 , Yingjian Lu  2
Affiliations

Ameliorated effects of a lipopeptide surfactin on insulin resistance in vitro and in vivo

Xiaoyu Chen et al. Food Sci Nutr. .

Abstract

Surfactin, produced by Bacillus amyloliquefaciens fmb50, was used to treat insulin-resistant (IR) hepatocyte. It was found that surfactin increased glucose consumption in insulin-resistant HepG2 (IR-HepG2) cells and ameliorated IR by increasing glucose transporter 4 (GLUT4) protein expression and AMP-activated protein kinase (AMPK) mRNA expression, promoting GLUT4 translocation and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in IR-HepG2 cells. Meanwhile, surfactin downregulated protein expression of phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase), further inhibiting hepatic gluconeogenesis. In addition, surfactin played important roles in eliminating reactive oxygen species (ROS), improving mitochondrial dysfunction, and inhibiting proinflammatory mediators. We observed that surfactin promoted glucose consumption, meanwhile increased translocation and protein expression of GLUT4 in Caco-2 cells. These results confirmed the conclusion in hepatic cells. Furthermore, surfactin supplement decreased body weight, food intake, and fasting blood glucose of type 2 diabetes mellitus (T2DM) mice induced by streptozotocin (STZ)/high-fat diet (HFD). Our data indicated that surfactin ameliorated insulin resistance and lowered blood glucose in intro and in vivo.

Keywords: GLUT4; PI3K/Akt pathway; inflammation; insulin resistance; oxidative stress; surfactin.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

FIGURE 1
FIGURE 1
Effect of surfactin on cell viability and glucose consumption in IR‐HepG2. (a) Cell viability with different concentrations (0–100 μg/ml) of surfactin for 48 h. (b) Cell viability with insulin (15 μg/ml) and different concentrations (6.25–25 μg/ml) of surfactin for 48 h. (c) Glucose consumption with insulin (15 μg/ml) and different concentrations (6.25–25 μg/ml) of surfactin for 48 h. All data are expressed as mean ± SD (n = 6) for each group. Different lowercase alphabet letters were significantly different at level of p < .05
FIGURE 2
FIGURE 2
Effects of surfactin on gluconeogenesis‐related enzymes and GLUT4 translocation in IR‐HepG2 cells. (a) The protein expression of G6pase. (b) The protein expression of PEPCK. (c) The protein expression of GLUT4. (d) The GLUT4 translocation. (e) Representative images of immunofluorescence staining of GLUT4. (f) The corresponding relative fluorescence intensity of GLUT4. All data are presented as mean ± SD (n = 3) for each group. Different lowercase alphabet letters over bars indicate statistically significant differences between two groups (p < .05)
FIGURE 3
FIGURE 3
Effects of surfactin on mRNA expression levels of key genes in insulin signaling pathway and gluconeogenesis in IR‐HepG2 cells. (a) The mRNA expression of PI3K. (b) The mRNA expression of Akt. (c) The mRNA expression of AMPK. (d) The protein expression of AMPK. (e) The mRNA expression of regulator of GLUT4. (f) The mRNA expression of GLUT4. (g) The mRNA expression of HNF4α. All data are presented as mean ± SD, (n ≥ 3) for each group. Different lowercase alphabet letters over bars indicate statistically significant differences between two groups (p < .05)
FIGURE 4
FIGURE 4
Effects of surfactin on key protein in insulin signaling pathway in IR‐HepG2 cells. (a) The western blot analysis. (b) The protein expression of PI3K. (c) The protein expression of Akt. (d) The protein expression of AMPK. (e) The ratio of p‐PI3K to PI3K. (f) The ratio of p‐Akt to Akt. (g) The ratio of p‐AMPK to AMPK. All data are presented as mean ± SD (n ≥ 3) for each group. Different lowercase alphabet letters over bars indicate statistically significant differences between two groups (p < .05)
FIGURE 5
FIGURE 5
Effects of surfactin on ROS generation and mitochondrial membrane potential in IR‐HepG2 cells. (a) The mean fluorescence intensity reflects intracellular ROS level (104−106). (b) The corresponding histograms of DCFH‐DA fluorescence intensity. (c) Fluorescence images of JC‐1 aggregates and JC‐1 monomers. (d) Relative mitochondrial membrane potential after calculation of the ratio of JC‐1 aggregates to JC‐1 monomers. All data are presented as mean ± SD (n ≥ 3) for each group. Different lowercase alphabet letters over bars indicate statistically significant differences between two groups (p < .05)
FIGURE 6
FIGURE 6
Effects of surfactin on mRNA and protein expression level of proinflammatory factors associated with insulin resistance signaling pathway in IR‐HepG2 cells. (a) The mRNA expression of IL‐1β. (b) The protein expression of IL‐1β. (c) The mRNA expression of IL‐6. (d) The mRNA expression of TNF‐α. All data are presented as mean ± SD (n = 6) for each group. Different lowercase alphabet letters over bars indicate statistically significant differences between two groups (p < .05)
FIGURE 7
FIGURE 7
Effect of surfactin on cell viability and glucose consumption in Caco‐2 cells. (a) Cell viability with different concentrations (0–100 μg/ml) of surfactin for 48 h. (b) Glucose consumption without and with surfactin for 48 h. All data are expressed as mean ± SD (n = 6) for each group. Different lowercase alphabet letters were significantly different at level of p < .05
FIGURE 8
FIGURE 8
Effects of surfactin on GLUT4, its translocation, and mitochondrial membrane potential in Caco‐2 cells. (a) The protein expression of GLUT4. (b) The mRNA expression of GLUT4. (c) The mRNA expression of regulator of GLUT4. (d) The GLUT4 translocation. (e) Representative images of immunofluorescence staining of GLUT4. (f) The corresponding relative fluorescence intensity of GLUT4. All data are presented as mean ± SD (n ≥ 3) for each group. Different lowercase alphabet letters over bars indicate statistically significant differences between two groups (p < .05)
FIGURE 9
FIGURE 9
Effects of surfactin on body weight, food intake, and fasting blood glucose of T2DM mice induced by STZ/HFD. (a) Body weight. (b) Food intake. (c) Fasting blood glucose. All data are presented as mean ± SD (n = 10) for each group. *Indicates statistically significant differences between the control group and the T2DM group (p < .05). #Indicates statistically significant differences between the T2DM and surfactin supplement group (p < .05)
FIGURE 10
FIGURE 10
Underlying and hypothesis of molecular mechanism ameliorating IR of surfactin in IR‐HepG2 cells. Red arrows denote changes in response to high insulin, and green arrows denote changes in high insulin‐induced cells receiving surfactin intervention
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References

    1. Chandel, N. S. (2015). Evolution of mitochondria as signaling organelles. Cell Metabolism, 22(2), 204–206. 10.1016/j.cmet.2015.05.013 - DOI - PubMed
    1. Chen, Z. Q. , Li, W. W. , Guo, Q. W. , Xu, L. L. , Santhanama, R. K. , Gao, X. D. , Chen, Y. , Wang, C. L. , Panichayupakaranant, P. , & Chen, H. X. (2019). Anthocyanins from dietary black soybean potentiate glucose uptake in L6 rat skeletal muscle cells via up‐regulating phosphorylated Akt and GLUT4. Journal of Functional Foods, 52, 663–669. 10.1016/j.jff.2018.11.049 - DOI
    1. Choi, S. S. , Cha, B. Y. , Iida, K. , Lee, Y. S. , Yonezawa, T. , Teruya, T. , Nagai, K. , & Woo, J. T. (2011). Artepillin C, as a PPARγ ligand, enhances adipocyte differentiation and glucose uptake in 3T3‐L1 cells. Biochemical Pharmacology, 81(7), 925–933. - PubMed
    1. Dilna, S. V. , Surya, H. , Aswathy, R. G. , Varsha, K. K. , Sakthikumar, D. N. , Pandey, A. , & Nampoothiri, K. M. (2015). Characterization of an exopolysaccharide with potential health‐benefit properties from a probiotic Lactobacillus plantarum RJF4. LWT‐Food Science and Technology, 64(2), 1179–1186. 10.1016/j.lwt.2015.07.040 - DOI
    1. Du, D. , Shi, Y. H. , & Le, G. W. (2010). Oxidative stress induced by high‐glucose diet in liver of C57BL/6J mice and its underlying mechanism. Molecular Biology Reports, 37, 3833–3839. 10.1007/s11033-010-0039-9 - DOI - PubMed

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